This project focuses on developing and validating an MRI-based method to measure regional myocardial oxygen consumption (MVO2). Since regulation of myocardial blood flow in the normal heart is closely linked to oxygen demand, MVO2 represents an essential parameter for understanding the additional competing mechanisms of flow regulation in health and disease. MVO2 has been shown to provide a critical parameter for identifying potentially salvageable myocardium from irreversibly injured tissue in ischemic disease. Failure of the heart to convert oxygen into work is found in various forms of ventricular dysfunction unrelated to coronary disease (hypertrophy, cardiomyopathy). With the availability of new drugs for the treatment of heart failure, there is a growing need for monitoring their effects on cardiac efficiency. MVO2 measurement provides a key component for evaluating the metabolic cost of ventricular work and thus, can improve our ability to optimize drug therapy. In the proposed research, we will extend to the heart recently developed MRI methods that have been used to estimate oxygen consumption in the brain. We will implement, optimize, and validate these methods in a closed-chest porcine model of normal heart. In Aim 1, optimizations include improved fast imaging techniques to more robustly measure T1-based flow and T2-based oxygenation dependent images of the beating heart. In Aim 2, we will compare the dynamic sensitivity of intravascular contrast agent-based measurements of myocardial blood volume volume and endogenous T1-based measurements of myocardial blood flow. In Aim 3, will optimize the calibration of the T2-based oxygenation signal (BOLD) in the myocardium. In Aim 4, MRI measurements of myocardial oxygenation and hemodynamics will be combined and myocardial oxygen consumption will be examined at rest and under various cardiac workloads. The MRI-estimated MVO2 will be compared to invasive measurements of global MVO2 using radiolabeled microsphere injection (perfusion) and arterial/venous blood sampling (blood oxygenation and hematocrit) and Fick's Law. Our overall hypothesis is that MRI measurements-BOLD signal, myocardial blood flow and myocardial blood volume - can be combined together to enable regional estimation of steady-state MVO2. Although the long-term goal of our work is to use MVO2 measurement for patient studies, the scope of the present grant focuses on an animal model in order to completely characterize the physiology and permit validation using invasive methods. We believe that the proposed measurements of MVO2 will provide a critical research tool for exploring non-invasively the relationship between local metabolism and contractile function in normal and diseased states. Ultimately, the proposed method may provide both hemodynamic and metabolic components or an integrated cardiac MRI exam in the assessment of hear disease.